Trop2 inhibits proliferation and promotes cell survival in low serum conditions in breast cancer cells
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Carcinomas account for 80-90% of all tumors. Trop2 is transmembrane glycoprotein commonly overexpressed in carcinomas where its expression often correlates with tumor aggressiveness, metastases, and poor prognosis. Trop2 is therefore considered as suitable antigen for targeted therapy. Interestingly, our knowledge about molecular mechanisms of Trop2 action in cancer cells is limited. Using overexpression of wt and mutant Trop2 proteins, we have investigated the role of Trop2 in cell response to stress in MDA-MB-231 breast cancer cell line. Our data show that cells overexpressing Trop2 are more resistant to starvation that corresponds to their lower proliferation activity and activation of Akt kinase. Moreover, we found that Akt activation depends on Trop2 regulated intramembrane proteolysis. Our findings provide a novel insight into Trop2 signaling and function in cancer cells with potential implications for future research and therapies. This work was supported by the projects no. LQ1605 from the National Program of Sustainability II (MEYS Czech Republic), and MUNI/A/0824/2017 from Grant Agency of the Masaryk University.